Formation of non-amidine products in the reaction of primary amines with imido esters

Abstract

Imido esters are widely employed for the chemical modification of amino groups in proteins between pH 7–10. We have found that near pH 8 the initial products of reaction of simple primary amines with imido esters are N-alkyl imidates which subsequently react either with ammonia to yield the expected amidine or with water to form free amine. In contrast, near pH 10 amidine formation occurs more rapidly and in better yield, apparently without the accumulation of an intermediate. The observed mechanism of amidine formation implies the possible occurrence of novel side reactions and suggests improved conditions for protein amidination.